Nonspecific Intraventricular Conduction Delay

Nonspecific intraventricular conduction delay (IVCD) is a QRS duration of 110 ms or more that meets the criteria for none of left bundle branch block, right bundle branch block or fascicular block. The QRS is widened with an atypical, variable morphology and no single bundle pattern.

Studies of resynchronisation use the stricter threshold of 120 ms or more. It is uncommon in healthy adults and becomes more frequent with age, hypertension, left ventricular hypertrophy, cardiomyopathy and heart failure.

Myocardial causes are diffuse fibrosis, left ventricular dilatation or hypertrophy, ischaemic scar with peri-infarction block, infiltrative disease (amyloidosis, sarcoidosis), myocarditis, Chagas disease, arrhythmogenic cardiomyopathy with parietal block, and LMNA or SCN5A cardiomyopathy.

Reversible causes are hyperkalaemia, acidosis, hypothermia, severe hypoxia, and sodium channel blocking drugs (class IA and IC antiarrhythmics, tricyclic antidepressants, diphenhydramine, chloroquine, cocaine, local anaesthetic toxicity).

Pathophysiology. Slow or uneven impulse spread through the Purkinje network and ventricular muscle (fibrosis, hypertrophy, scar or sodium current blockade) lengthens ventricular activation without any single bundle being at fault.

The wide QRS reflects dyssynchronous activation and alters repolarisation, giving secondary ST-T change. In heart failure QRS duration tracks mortality, and benefit from cardiac resynchronisation is smaller than with left bundle branch block, because the delay is usually diffuse and not at one site.

In sodium channel blocker toxicity, QRS widening is dose related. A QRS over 100 ms predicts seizures and a QRS over 160 ms predicts ventricular arrhythmia.

Most patients are asymptomatic and the diagnosis is made on ECG. Symptoms come from the cause: exertional dyspnoea, orthopnoea and oedema in cardiomyopathy; angina in ischaemic disease; palpitations or syncope from ventricular arrhythmia or infra-Hisian block. Sodium channel blocker toxicity causes agitation, seizures, dilated pupils, dry mucosae, sinus tachycardia and hypotension. Hyperkalaemia causes weakness and paraesthesia. Examination is normal or shows the signs of the underlying disease, with a normally split or mildly widened second heart sound.

Red flags.

• QRS widening of over 25% from a previous tracing
• QRS over 100 ms after a possible overdose of a sodium channel blocker
• Syncope or presyncope
• Ejection fraction of 35% or less with a QRS of 150 ms or more
• Peaked T waves, loss of P waves or a sine wave pattern (hyperkalaemia)
• Epsilon waves, T wave inversion in V1 to V3, or sudden death in a relative under 40 years
• Ventricular tachycardia, or atrioventricular block in a young patient

• 12-lead ECG. Measure QRS from the earliest onset to the latest end in any lead. Confirm that left bundle branch block, right bundle branch block, fascicular block, pre-excitation and ventricular pacing are absent. Compare with old tracings, because new widening matters more than the absolute value.
• Laboratory. Potassium, calcium, magnesium, blood gas and bicarbonate, creatinine, troponin, natriuretic peptide, thyroid function, and a toxicology screen or tricyclic antidepressant and digoxin levels when poisoning is possible.
• Echocardiography. Chamber size, wall thickness, ejection fraction, regional wall motion, valve disease, dyssynchrony, and infiltrative features.
• Cardiac MRI with late gadolinium enhancement. Scar, diffuse fibrosis, infiltration and right ventricular disease, in patients with reduced ejection fraction, young age or an unexplained cause.
• Ischaemia assessment by stress imaging or CT or invasive coronary angiography when symptoms or risk factors warrant.
• Ambulatory ECG or implantable loop recorder for paroxysmal atrioventricular block and ventricular arrhythmia.
• Electrophysiology study for unexplained syncope. An HV interval of 70 ms or more, or induced infra-Hisian block, indicates pacing. Inducible sustained monomorphic ventricular tachycardia indicates a defibrillator.
• Genetic testing when conduction disease or cardiomyopathy runs in the family (LMNA, SCN5A, desmosomal and other genes).

Differential diagnosis.

• Left bundle branch block and right bundle branch block with fascicular block
• Pre-excitation
• Ventricular paced rhythm
• Hyperkalaemia and drug induced QRS widening
• Left ventricular hypertrophy with mild QRS prolongation
• Ventricular rhythms: accelerated idioventricular rhythm, ventricular tachycardia, premature ventricular beats
• Brugada pattern
• Arrhythmogenic right ventricular cardiomyopathy

• Isolated IVCD, structurally normal heart, no symptoms: no treatment. One echocardiogram, control of blood pressure and cardiovascular risk, and a yearly ECG to track QRS duration.
• Reversible causes: stop the offending drug and correct acidosis, hypoxia and hypothermia.
• Sodium channel blocker toxicity with QRS over 100 ms, arrhythmia or hypotension: sodium bicarbonate 1 to 2 mmol/kg intravenously (8.4% solution, 1 mmol/mL) as a bolus over 1 to 2 minutes, repeated every 3 to 5 minutes until the QRS is under 100 ms. Aim for blood pH 7.45 to 7.55 and do not exceed 7.55. If the QRS widens again, infuse 150 mmol in 1 litre of 5% glucose at 100 to 250 mL/h. Monitor pH, potassium, sodium and ionised calcium, and watch for hypokalaemia and fluid overload. Avoid class IA, IC and III antiarrhythmics.
• Hyperkalaemia with QRS widening:
  • Calcium gluconate 10% 30 mL intravenously over 10 minutes with continuous ECG monitoring, repeated once after 10 minutes if ECG changes persist.
  • Soluble insulin 10 units with glucose 25 g (50 mL of 50% glucose) intravenously over 15 minutes. Use 5 units in severe renal impairment or low body weight. Check capillary glucose hourly for 6 hours.
  • Salbutamol 10 to 20 mg nebulised over 10 minutes as an adjunct. Avoid in unstable angina or tachyarrhythmia.
  • Stop potassium raising drugs. Dialysis for refractory cases or renal failure.
• Heart failure with reduced ejection fraction (40% or less): full tolerated medical therapy for at least 3 months before any device decision.
  • Sacubitril/valsartan 49/51 mg orally twice daily, doubled at 2 to 4 weeks to the target 97/103 mg twice daily (maximum 194/206 mg daily). Start 24/26 mg twice daily if not on an ACE inhibitor or angiotensin receptor blocker, on low doses, with eGFR under 30 mL/min/1.73 m2, or with moderate liver impairment. Stop any ACE inhibitor 36 hours before. Contraindicated with previous angio oedema, severe liver impairment and pregnancy. Check potassium and creatinine 1 to 2 weeks after each change.
  • Bisoprolol 1.25 mg orally once daily, increased every 1 to 4 weeks to the target 10 mg once daily, maximum 10 mg daily in heart failure. Contraindicated in cardiogenic shock, second or third degree atrioventricular block without a pacemaker, sick sinus syndrome and severe asthma.
  • Spironolactone 25 mg orally once daily (12.5 mg at eGFR 30 to 49 mL/min/1.73 m2), up to 50 mg daily. Check potassium and creatinine at 1 week and 4 weeks, then every 3 months. Withhold at potassium over 5.5 mmol/L and avoid at eGFR under 30 mL/min/1.73 m2.
  • Dapagliflozin 10 mg orally once daily, long term. Start at eGFR 25 mL/min/1.73 m2 or more. Withhold during acute illness with poor oral intake. Contraindicated in type 1 diabetes.
• Cardiac resynchronisation therapy: considered when ejection fraction is 35% or less, NYHA class II to IV persists after 3 months of optimal therapy, rhythm is sinus, and QRS is 150 ms or more. At 130 to 149 ms the evidence is weaker. Use a defibrillator capable device when defibrillator criteria are also met. Conduction system pacing is an alternative when coronary sinus lead placement fails.
• Unexplained syncope: electrophysiology study or implantable loop recorder, with pacing or a defibrillator as indicated by the electrophysiology findings.
• LMNA, desmosomal or infiltrative disease: these carry high arrhythmic risk, so assess early for a defibrillator even with ejection fraction over 35%, and refer for disease specific therapy.

Special groups. In pregnancy, stop sacubitril/valsartan, spironolactone and dapagliflozin before conception.

Monitoring. ECG yearly and with any new symptom. Echocardiography at 3 months after each heart failure drug titration. Potassium, creatinine and blood pressure after each titration. Device checks every 3 to 6 months with remote monitoring, aiming for biventricular pacing over 98%.

Referral and escalation. Refer to cardiology for new or progressive QRS widening, and to electrophysiology for syncope, ejection fraction of 35% or less, or atrioventricular block. Urgent for syncope, QRS widening with hyperkalaemia or poisoning, or ventricular arrhythmia.